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Haemocompatibility (The clotting process (Platelet activation and…

- - - - Increased shear
    - - Large, multimeric protein
      - Monomers contain binding domains for proteins
      - Activated at a certain rate of fluid flow
      - Chains unfold and monomers expose binding domain
      - Critical rate equation
    - - Stretches protein
      - Shear flow is too low for unfolding of vWF
      - Response to elongational flow is sharper
  - - - Calcuim
      - Fibrinogen
      - vWF
      - Clotting factors
    - - Binds prothrombin
  - - - Extrinsic
        
        Response to tissue injury
        
        Driven by the generation of tissue factor (TF)
      - Intrinsic
        
        Response to abnormal vessel
        wall or endothelial damage
        
        Exposure of collagen fibres activates factor XII
    - - Factor Xa + Ca2+ catalyse prothrombin -> thrombin
      - Thrombin + Ca2+ converts fibrinogen to fibrin threads
      - Cross linking to form insoluble gel network
      - Gel stabilises platelets against mechanical stress
- - - - Complications
        
        Damage to endothelium
        
        Inflammation
        
        Blood clotting
        
        Outgrowth of SMC & collagen
        
        Reduced lumen
        
        Metal in the wall
        promotes
        
        Migration and proliferation of SMC
        
        Increased ECM
      - Stabilise the structure of a vessel
      - Clear the lumen of an artery
      - Design considerations
        
        Strength
        
        Fatigue
        
        Deliverability
        
        Arterial wall interaction
        
        Haemodynamics
        
        Induction of endothelialisation
      - Drug eluting stents
        
        Antithrombotic & antirestinosis drugs
        
        Antiplatelet drugs
        
        Calcuim agonists
        
        Antiinflammatory drugs
        
        Antiproliferative drugs
        
        Structure modification -> controlled drug release
        
        Biodegradable polymers allow regrowth
  - - - Albumin
        
        Reduces platelet and leukocyte adhesion
        
        Inhibits thrombus formation
        
        Inhibits fibrin formation
        
        Negatively charged
      - Heparin
        
        Activates antithrombin III
        
        Used as a coating material
    - - Contact of blood and synthetic surface
      - -ve surfaces particularly prone
    - - TF present after damage
      - Subendothelial cells
  - - - Ratiation therapy
      - Gene therapy
      - Drug-eluting polymer coating
- - - - Albumin
      - Immunoglobulins
      - Fibrinogen
    - - Ions
      - Nutrients
      - Waste products
      - Gases
      - Regulatory substances
  - - - Small discoidal cells
      - Anucleated
      - Work with coagulation factors
      - Essential to the clotting process
    - - 2 types
        
        Acquired immunity
        
        Eosinophils
        
        Basophils
        
        Lymphocytes
        
        Innate immunity
        
        Monocytes
        
        Neutrophils
      - Part of the immune system
    - - Anucleated cells
      - Contain haemoglobin
      - Can deform to squeeze through capillaries
      - Flattened disc shape